Mechanism Matters: Differential benefits of cold-stored whole blood for trauma resuscitation from a prospective multicenter study.

BACKGROUND: Resuscitation with cold-stored low-titre whole blood (LTOWB) has increased despite the paucity of robust civilian data. Most studies are in predominately blunt trauma and lack analysis of specific subgroups or mechanism of injury. We sought to compare outcomes between patients receiving LTOWB vs. balanced component therapy (BCT) after blunt (BL) and penetrating (PN) trauma. METHODS: Secondary analysis of a prospective multicenter study of patients receiving either LTWOB-containing or BCT resuscitation was performed. Patients were grouped by mechanism of injury (BL vs PN). A generalized estimated equations model using inverse probability of treatment weighting was employed. Primary outcome was mortality and secondary outcomes were acute kidney injury, venous thromboembolism, pulmonary complications, and bleeding complications. Additional analyses were performed on non-traumatic brain injury (TBI), severe torso injury, and LTOWB-only resuscitation patients. RESULTS: 1617 patients (BL 47% vs PN 54%) were identified; 1175 (73%) of which received LTOWB. PN trauma patients receiving LTOWB demonstrated improved survival compared to BCT (77% vs. 56%; p<0.01). Interval survival was higher at 6 hrs (95% vs. 88%), 12 hrs (93% vs. 80%) and 24 hrs (88% vs. 57%) (all p<0.05). The survival benefit following LTOWB was also seen across PN non-TBI (83% vs. 52%), and severe torso injuries (75% vs. 43%) (all p <0.05). After controlling for age, sex, injury severity, and trauma center, LTWOB was associated with decreased odds of death (OR .31, p<.05) in PN trauma. However, no difference in overall mortality was seen across the BL groups. Both PN and BL patients receiving LTOWB had more frequent AKI compared to BCT (19% vs. 7% and 12% vs 6%, respectively; p<0.05). CONCLUSIONS: LTOWB resuscitation was independently associated with decreased mortality following PN trauma, but not BL trauma. Further analysis in BL trauma is required to identify subgroups that may demonstrate survival benefit. LEVEL OF EVIDENCE: Therapeutic/Care Management, III.

Gender diversity in radiology: Shedding light on the 256 shades of grey.

INTRODUCTION: Despite medical school cohorts being composed of approximately 50% men and women, trainee positions in Clinical Radiology remain predominantly occupied by men. This study aims to identify reasons behind the gender gap, explore why more women are not pursuing a career in Clinical Radiology and to assess if there are gender differences in these reasons. METHODS: Prospective multi-centre study using a voluntary, anonymous questionnaire aimed at senior Medical Students and Junior Doctors. RESULTS: A total of 318 participants responded to the questionnaire - 197 women (61.9%), 114 men (35.8%), 4 non-binary (1.3%), 2 preferred not to answer gender (0.6%), 1 I/they (0.3%). The most common reasons for not considering Clinical Radiology as a specialty include 'perceived limited patient contact' (62%), 'never/rarely exposed to it' (59%) and 'too lonely' (49%). Reasons with the largest gender discrepancies were 'too technology heavy' and 'limited patient contact', both cited more frequently by women. Most respondents indicated that their opinions of Clinical Radiology may change with more exposure during medical school, more patient contact and more mentorship. CONCLUSION: This study has revealed multiple reasons why women may not pursue specialty training in Clinical Radiology. Notable differences were found in the reasonings provided by men and women. Limited Clinical Radiology exposure and mentorship in medical school result in a lack of interest in this specialty as a career option. A proposed solution is to offer more medical school lectures and more junior doctor rotations to debunk stereotypes that may be negatively impacting opinions on Clinical Radiology. More mentorship of Medical Students and Junior Doctors, particularly from women, may also help decrease the gender gap.

COVID-19 and Mortality in the Global Surgical Population: A Systematic Review and Meta-Analysis.

INTRODUCTION: To date, no systematic review or meta-analysis has comprehensively estimated the risk of mortality by surgery type on an international scale. We aim to delineate the risk of mortality in patients with COVID-19 who undergo surgery. METHODS: PubMed (MEDLINE), Scopus, OVID, the World Health Organization Global Literature on Coronavirus Disease, and Corona-Central databases were searched from December 2019 through January 2022. Studies providing data on mortality in patients undergoing surgery were included. The Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines for abstracting data were followed and performed independently by two reviewers. The main outcome was mortality in patients with COVID-19. RESULTS: Of a total of 4023 studies identified, 46 studies with 80,015 patients met our inclusion criteria. The mean age was 67 y; 57% were male. Surgery types included general (14.9%), orthopedic (23.4%), vascular (6.4%), thoracic (10.6%), and urologic (8.5%). Patients undergoing surgery with COVID-19 elicited a nine-fold increased risk of mortality (relative risk [RR] 8.99, 95% confidence interval [CI] 4.96-16.32) over those without COVID-19. In low-income and middle-income countries (RR: 16.04, 95% CI: 4.59-56.12), the mortality risk was twice as high compared to high-income countries (RR: 7.50, 95% CI: 4.30-13.09). CONCLUSIONS: Mortality risk in surgical patients with COVID-19 compared to those without is increased almost 10-fold. The risk was highest in low-income and middle-income countries compared to high-income countries, suggesting a disproportionate effect of the pandemic on resource-constrained regions.

The Application of Knowledge-Based Clinical Decision Support Systems to Detect Antibiotic Allergy.

Prevention of drug allergies is important for patient safety. The objective of this study was to evaluate the outcomes of antibiotic allergy-checking clinical decision support system (CDSS), K-CDSTM. A retrospective chart review study was performed in 29 hospitals and antibiotic allergy alerts data were collected from May to August 2022. A total of 15,535 allergy alert cases from 1586 patients were reviewed. The most frequently prescribed antibiotics were cephalosporins (48.5%), and there were more alerts of potential cross-reactivity between beta-lactam antibiotics than between antibiotics with the same ingredients or of the same class. Regarding allergy symptoms, dermatological disorders were the most common (38.8%), followed by gastrointestinal disorders (28.4%). The 714 cases (4.5%) of immune system disorders included 222 cases of anaphylaxis and 61 cases of severe cutaneous adverse reactions. Alerts for severe symptoms were reported in 6.4% of all cases. This study confirmed that K-CDS can effectively detect antibiotic allergies and prevent the prescription of potentially allergy-causing antibiotics among patients with a history of antibiotic allergies. If K-CDS is expanded to medical institutions nationwide in the future, it can prevent an increase in allergy recurrence related to drug prescriptions through cloud-based allergy detection CDSSs.

The Role of MAPRE2 and Microtubules in Maintaining Normal Ventricular Conduction.

BACKGROUND: Brugada syndrome is associated with loss-of-function SCN5A variants, yet these account for only ≈20% of cases. A recent genome-wide association study identified a novel locus within MAPRE2, which encodes EB2 (microtubule end-binding protein 2), implicating microtubule involvement in Brugada syndrome. METHODS: A mapre2 knockout zebrafish model was generated using CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/clustered regularly interspaced short palindromic repeat-associated protein 9) and validated by Western blot. Larval hearts at 5 days post-fertilization were isolated for voltage mapping and immunocytochemistry. Adult fish hearts were used for ECG, patch clamping, and immunocytochemistry. Morpholinos were injected into embryos at 1-cell stage for knockdown experiments. A transgenic zebrafish line with cdh2 tandem fluorescent timer was used to study adherens junctions. Microtubule plus-end tracking and patch clamping were performed in human induced pluripotent stem cell derived cardiomyocytes (iPSC-CMs) with MAPRE2 knockdown and knockout, respectively. RESULTS: Voltage mapping of mapre2 knockout hearts showed a decrease in ventricular maximum upstroke velocity of the action potential and conduction velocity, suggesting loss of cardiac voltage-gated sodium channel function. ECG showed QRS prolongation in adult knockout fish, and patch clamping showed decreased sodium current density in knockout ventricular myocytes and arrhythmias in knockout iPSC-CMs. Confocal imaging showed disorganized adherens junctions and mislocalization of mature Ncad (N-cadherin) with mapre2 loss of function, associated with a decrease of detyrosinated tubulin. MAPRE2 knockdown in iPSC-CMs led to an increase in microtubule growth velocity and distance, indicating changes in microtubule dynamics. Finally, knockdown of ttl encoding tubulin tyrosine ligase in mapre2 knockout larvae rescued tubulin detyrosination and ventricular maximum upstroke velocity of the action potential. CONCLUSIONS: Genetic ablation of mapre2 led to a decrease in voltage-gated sodium channel function, a hallmark of Brugada syndrome, associated with disruption of adherens junctions, decrease of detyrosinated tubulin as a marker of microtubule stability, and changes in microtubule dynamics. Restoration of the detyrosinated tubulin fraction with ttl knockdown led to rescue of voltage-gated sodium channel-related functional parameters in mapre2 knockout hearts. Taken together, our study implicates microtubule dynamics in the modulation of ventricular conduction.

Novel cross-linked polysaccharide-polyelectrolyte hemostatic foam improves survival compared to CombatGauze in swine femoral artery hemorrhage model.

BACKGROUND: Uncontrolled hemorrhage is the leading cause of preventable death in combat and civilian trauma. Efficacious hemostatic agents in junctional hemorrhage can quell blood loss and improve survival. We hypothesized that a novel hemostatic foam of starch and chitosan would improve hemostasis, and thereby increase survival in a swine femoral artery hemorrhage model when compared with CombatGauze (CG). METHODS: A novel hemostatic foam of starch and chitosan was created and modified during the study period. Thirty pigs (four excluded) were assigned to treatment using either foam version 1 (FV1, n = 9) or 2 (FV2, n = 8), or (n = 9) in a standard swine femoral artery hemorrhage model. Animals were observed for 150 minutes. Outcomes assessed included hemostasis, survival, posttreatment blood loss, IV fluid volume, and hemodynamic and laboratory trends. RESULTS: Hemostasis prior to 150 minutes was similar with 44.4%, 77.8%, and 50% of swine treated with CG, FV1 and FV2, respectively (Kaplan-Meyer and log-rank test [KM-LR] p > 0.05). Survival to 150 minutes was improved in swine treated with FV1 (100%) compared with CG (55.6%) (KM-LR p = 0.02). Survival was similar between FV1 and FV2 (75%) (KM-LR p > 0.05), and between CG and FV2 (KM-LR p > 0.05). Using mixed model for longitudinal data, mean arterial pressure decreased significantly in CG- and FV2-treated swine, while there was no significant change in mean arterial pressure in FV1-treated swine. Trends in lactic acid, hematocrit, platelets, INR, and thrombelastography were more favorable for FV1 compared with CG. CONCLUSION: In this preclinical study of junctional hemorrhage, survival was improved in swine treated with version 1 of a novel chitosan/starch foam compared with CG. Trends in hemodynamics and laboratory data were also more favorable in the FV1-treated swine. This novel hemostatic foam may be an effective alternative to current hemostatic agents.

Use of Cold-Stored Whole Blood is Associated With Improved Mortality in Hemostatic Resuscitation of Major Bleeding: A Multicenter Study.

OBJECTIVE: The aim of this study was to identify a mortality benefit with the use of whole blood (WB) as part of the resuscitation of bleeding trauma patients. BACKGROUND: Blood component therapy (BCT) is the current standard for resuscitating trauma patients, with WB emerging as the blood product of choice. We hypothesized that the use of WB versus BCT alone would result in decreased mortality. METHODS: We performed a 14-center, prospective observational study of trauma patients who received WB versus BCT during their resuscitation. We applied a generalized linear mixed-effects model with a random effect and controlled for age, sex, mechanism of injury (MOI), and injury severity score. All patients who received blood as part of their initial resuscitation were included. Primary outcome was mortality and secondary outcomes included acute kidney injury, deep vein thrombosis/pulmonary embolism, pulmonary complications, and bleeding complications. RESULTS: A total of 1623 [WB: 1180 (74%), BCT: 443(27%)] patients who sustained penetrating (53%) or blunt (47%) injury were included. Patients who received WB had a higher shock index (0.98 vs 0.83), more comorbidities, and more blunt MOI (all P <0.05). After controlling for center, age, sex, MOI, and injury severity score, we found no differences in the rates of acute kidney injury, deep vein thrombosis/pulmonary embolism or pulmonary complications. WB patients were 9% less likely to experience bleeding complications and were 48% less likely to die than BCT patients ( P <0.0001). CONCLUSIONS: Compared with BCT, the use of WB was associated with a 48% reduction in mortality in trauma patients. Our study supports the use of WB use in the resuscitation of trauma patients.

The cost of treatments for retained traumatic hemothorax: A decision analysis.

INTRODUCTION: Early video-assisted thorascopic surgery (VATS) is the recommended intervention for retained hemothorax in trauma patients. Alternative options, such as lytic therapy, to avoid surgery remain controversial. The purpose of this decision analysis was to assess expected costs associated with treatment strategies. METHODS: A decision tree analysis estimated the expected costs of three initial treatment strategies: 1) VATS, 2) intrapleural tissue plasminogen activator (TPA) lytic therapy, and 3) intrapleural non-TPA lytic therapy. Probability parameters were estimated from published literature. Costs were based on National Inpatient Sample data and published estimates. Our model compared overall expected costs of admission for each strategy. Sensitivity analyses were conducted to explore the impact of parameter uncertainty on the optimal strategy. RESULTS: In the base case analysis, using TPA as the initial approach had the lowest total cost (U.S. $37,007) compared to VATS ($38,588). TPA remained the optimal initial approach regardless of the probability of complications after VATS. TPA was an optimal initial approach if TPA success rate was >83% regardless of the failure rate with VATS. VATS was the optimal initial strategy if its total cost of admission was <$33,900. CONCLUSION: Lower treatment costs with lytic therapy does not imply significantly lower total cost of trauma admission. However, an initial approach with TPA lytic therapy may be preferred for retained traumatic hemothorax to lower the total cost of admission given its high probability of avoiding the operating room with its resultant increased costs. Future studies should identify differences in quality of life after recovery from competing interventions.

Breast Cancer Survival in Eastern Region of Ghana.

Objective: Five-year overall survival rate of breast cancer in low-income countries (LICs) is significantly lower than in high-resource countries. This study explored clinical and pathological factors influencing mortality in the Eastern region of Ghana. Methods: We performed a retrospective medical chart review for patients undergoing surgery and chemotherapy for breast cancer at a regional hospital in Ghana from January 2014 to January 2017. Descriptive and survival analysis was done. Results: One hundred and twenty-nine patients were included in the study. The median age at presentation was 51 years. Sixty percent of patients presented with poorly differential histological grade III. The most common histological type was invasive ductal carcinoma (83%). Based on stage assessment using only tumor size and lymph node status, 60% presented at stage 3. Only 25% were tested for hormone receptor proteins and HER2 status. Of these, 57% had triple-negative breast cancer (TNBC). The 3-year overall survival rate was only 52%. Conclusion: The cumulative 3-year survival was 52%. Despite success in reducing cancer mortality in northern Africa, survival in sub-Saharan Africa remains poor. A significantly higher percentage of GIII and TNBC is found in breast cancers seen in Ghana. When combined with limited capacity for accurate diagnosis, cancer subtype analysis, adequate therapy, and follow-up, late-stage presentation leads to poor outcomes. Future studies should emphasize the identification of barriers to care and opportunities for cost-effective and sustainable improvements in diagnosing and treating breast cancer in LICs.

Mapping Cancer in Africa: A Comprehensive and Comparable Characterization of 34 Cancer Types Using Estimates From GLOBOCAN 2020.

Objective: Cancer incidence and mortality rates in Africa are increasing, yet their geographic distribution and determinants are incompletely characterized. The present study aims to establish the spatial epidemiology of cancer burden in Africa and delineate the association between cancer burden and the country-level socioeconomic status. The study also examines the forecasts of the cancer burden for 2040 and evaluates infrastructure availability across all African countries. Methods: The estimates of age, sex, and country-specific incidence and mortality of 34 neoplasms in 54 African countries, were procured from GLOBOCAN 2020. Mortality-to-incidence ratio (MIR) was employed as a proxy indicator of 5-year survival rates, and the socioeconomic development of each country was measured using its human development index (HDI). We regressed age-standardized incidence rate (ASIR), age-standardized mortality rate (ASMR), and MIR on HDI using linear regression model to determine the relationship between cancer burden and HDI. Maps were generated for each cancer group for each country in Africa. The data about the cancer infrastructure of African countries were extracted from the WHO Cancer Country Profiles. Results: In Africa, an estimated 1.1 million new cases [95% uncertainty intervals (UIs) 1.0 - 1.3 million] and 711,429 [611,604 - 827,547] deaths occurred due to neoplasms in 2020. The ASIR was estimated to be 132.1/100,000, varying from 78.4/100,000 (Niger) to 212.5/100,000 (La Réunion) in 2020. The ASMR was 88.8/100,000 in Africa, ranging from 56.6/100,000 in the Republic of the Congo to 139.4/100,000 in Zimbabwe. The MIR of all cancer combined was 0.64 in Africa, varying from 0.49 in Mauritius to 0.78 in The Gambia. HDI had a significant negative correlation with MIR of all cancer groups combined and main cancer groups (prostate, breast, cervical and colorectal). HDI explained 75% of the variation in overall 5-year cancer survival (MIR). By 2040, the burden of all neoplasms combined is forecasted to increase to 2.1 million new cases and 1.4 million deaths in Africa. Conclusion: High cancer mortality rates in Africa demand a holistic approach toward cancer control and management, including, but not limited to, boosting cancer awareness, adopting primary and secondary prevention, mitigating risk factors, improving cancer infrastructure and timely treatment.

Age-standardised incidence rate and epidemiology of colorectal cancer in Africa: a systematic review and meta-analysis.

OBJECTIVES: Colorectal cancer (CRC) is the second-leading cause of cancer deaths globally, with low-income and middle-income countries (LMICs) disproportionately affected. Estimates of CRC rates in LMIC are scarce. We aimed to (1) estimate sex-specific incidence of CRC, (2) estimate temporal trend and (3) determine regional variations of CRC rates on the African continent. DESIGN: Systematic review and meta-analysis METHODS: PubMed (MEDLINE), OVID (MEDLINE), Scopus and Cochrane Library databases were systematically searched from inception to 12 December 2020. We included population-based studies that reported the incidence or prevalence estimates of CRC in Africa. Studies not conducted in humans or did not directly report the rates of CRC were excluded. Random effects model was used to pool the estimates. The methodological quality of studies was assessed with the Newcastle-Ottawa Scale. OUTCOME MEASURES: Overall and sex-specific annual age-standardised incidence rates (ASIR) of CRC per 100 000 population. RESULTS: The meta-analysis included 14 studies consisting of 3365 individuals with CRC (mean age, 58 years, 53% male). The overall ASIR of CRC in Africa per 100 000 population was 5.25 (95% CI 4.08 to 6.75). The rates were slightly higher in males (4.76) than in females (4.18), but not significantly different. Subgroup analysis indicated greater point estimates in North Africa (8.66) compared with sub-Saharan Africa (5.91); and higher estimates in Eastern (8.29) and Northern (8.66) Africa compared with Western (3.55) and Southern (3.57) Africa, but not statistically significant. The overall trend in ASIR has remained constant at nearly 5 per 100 000 population for the last 6 decades. CONCLUSION: CRC estimates in Africa are heterogeneous and could be underestimated. High-quality data collection systems such as population-based cancer registries may facilitate accurate estimation of country-specific rates and provide critical information which would be lucrative to the consideration of resources needed for screening, early detection, treatment and improving overall patient outcomes.

Image-based assessment of sarcopenic obesity predicts mortality in major trauma.

BACKGROUND: Patients with obesity are also at risk for sarcopenia, which is difficult to recognize in this population. Our study examines whether sarcopenic-obesity (SO) is independently associated with mortality in trauma. METHODS: Using a retrospective database, we performed logistic regression analysis. . Admission CT scans were used to identify SO by calculating the visceral fat to skeletal muscle ratio >3.2. RESULTS: Of 883 patients, the prevalence of SO was 38% (333). Patients with SO were more likely to be male (79% versus 43%, p < 0.001), older (mean 66.5 years versus 46.3 years, p < 0.001), and less likely to have an injury severity score (ISS) ≥ 24 (43% versus 55%, p = 0.0003). Using multivariable logistic regression analysis, SO was independently associated with mortality (OR 2.8; 95% CI 1.6-4.8, p < 0.001). Causal mediation analysis found admission hyperglycemia as a mediator for mortality. CONCLUSIONS: Sarcopenic obesity is an independent predictor of mortality in major trauma.

Tranexamic acid administration and pulmonary embolism in combat casualties with orthopaedic injuries.

In combat casualty care, tranexamic acid (TXA) is administered as part of initial resuscitation effort; however, conflicting data exist as to whether TXA contributes to increased risk of venous thromboembolism (VTE). The purpose of this study is to determine what factors increase risk of pulmonary embolism after combat-related orthopaedic trauma and whether administration of TXA is an independent risk factor for major thromboembolic events. SETTING: United States Military Trauma Centers. PATIENTS: Combat casualties with orthopaedic injuries treated at any US military trauma center for traumatic injuries sustained from January 2011 through December 2015. In total, 493 patients were identified. INTERVENTION: None. MAIN OUTCOME MEASURES: Occurrence of major thromboembolic events, defined as segmental or greater pulmonary embolism or thromboembolism-associated pulseless electrical activity. RESULTS: Regression analysis revealed TXA administration, traumatic amputation, acute kidney failure, and hypertension to be associated with the development of a major thromboembolic event for all models. Injury characteristics independently associated with risk of major VTE were Injury Severity Score 23 or greater, traumatic amputation, and vertebral fracture. The best performing model utilized had an area under curve  = 0.84, a sensitivity=0.72, and a specificity=0.84. CONCLUSIONS: TXA is an independent risk factor for major VTE after combat-related Orthopaedic injury. Injury factors including severe trauma, major extremity amputation, and vertebral fracture should prompt suspicion for increased risk of major thromboembolic events and increased threshold for TXA use if no major hemorrhage is present. LEVEL OF EVIDENCE: III, Prognostic Study.

Whole blood versus component therapy for haemostatic resuscitation of major bleeding: a protocol for a systematic review and meta-analysis.

INTRODUCTION: There is a renewed interest in the use of whole blood (WB) to manage patients with life-threatening bleeding. We aimed to estimate mortality and complications risk between WB and blood component therapy for haemostatic resuscitation of major bleeding. METHODS: We will conduct a systematic review and meta-analysis of studies published between 1 January 1980 and 1 January 2020, identified from PubMed and Scopus databases. Population will be patients who require blood transfusion (traumatic operative, obstetric and gastrointestinal bleeding). Intervention is WB transfusion such as fresh WB (WB unit stored for less than 48 hours), leukoreduced modified WB (with platelets removed during filtration), warm fresh WB (stored warm at 22°C for up to 8 hours and then for a maximum of an additional 24 hours at 4°C). The primary outcomes will be the 24-hour and 30-day survival rates (in-hospital mortality). Comparator is blood component therapy (red blood cells, fresh-frozen plasma and platelets given together in a 1:1:1 unit ratio). The Cochrane risk of bias tool for randomised controlled trials and Risk Of Bias In Non-randomised Studies - of Interventions (ROBINS-I) for observation studies will be used to assess the risk of bias of included studies. We will use random-effects models for the pooling of studies. Interstudy heterogeneity will be assessed by the Cochran Q statistic, where p<0.10 will be considered statistically significant and quantified by I2 statistic, where I2 ≥50% will indicate substantial heterogeneity. We will perform subgroup and meta-regression analyses to assess geographical differences and other study-level factors explaining variations in the reported mortality risk. Results will be reported as risk ratios and their 95% CIs. ETHICS AND DISSEMINATION: No ethics clearance is required as no primary data will be collected. The results will be presented at scientific conferences and published in a peer-reviewed journal.

Short-term and Long-term Rates of Postacute Sequelae of SARS-CoV-2 Infection: A Systematic Review.

Importance: Short-term and long-term persistent postacute sequelae of COVID-19 (PASC) have not been systematically evaluated. The incidence and evolution of PASC are dependent on time from infection, organ systems and tissue affected, vaccination status, variant of the virus, and geographic region. Objective: To estimate organ system-specific frequency and evolution of PASC. Evidence Review: PubMed (MEDLINE), Scopus, the World Health Organization Global Literature on Coronavirus Disease, and CoronaCentral databases were searched from December 2019 through March 2021. A total of 2100 studies were identified from databases and through cited references. Studies providing data on PASC in children and adults were included. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines for abstracting data were followed and performed independently by 2 reviewers. Quality was assessed using the Newcastle-Ottawa Scale for cohort studies. The main outcome was frequency of PASC diagnosed by (1) laboratory investigation, (2) radiologic pathology, and (3) clinical signs and symptoms. PASC were classified by organ system, ie, neurologic; cardiovascular; respiratory; digestive; dermatologic; and ear, nose, and throat as well as mental health, constitutional symptoms, and functional mobility. Findings: From a total of 2100 studies identified, 57 studies with 250 351 survivors of COVID-19 met inclusion criteria. The mean (SD) age of survivors was 54.4 (8.9) years, 140 196 (56%) were male, and 197 777 (79%) were hospitalized during acute COVID-19. High-income countries contributed 45 studies (79%). The median (IQR) proportion of COVID-19 survivors experiencing at least 1 PASC was 54.0% (45.0%-69.0%; 13 studies) at 1 month (short-term), 55.0% (34.8%-65.5%; 38 studies) at 2 to 5 months (intermediate-term), and 54.0% (31.0%-67.0%; 9 studies) at 6 or more months (long-term). Most prevalent pulmonary sequelae, neurologic disorders, mental health disorders, functional mobility impairments, and general and constitutional symptoms were chest imaging abnormality (median [IQR], 62.2% [45.8%-76.5%]), difficulty concentrating (median [IQR], 23.8% [20.4%-25.9%]), generalized anxiety disorder (median [IQR], 29.6% [14.0%-44.0%]), general functional impairments (median [IQR], 44.0% [23.4%-62.6%]), and fatigue or muscle weakness (median [IQR], 37.5% [25.4%-54.5%]), respectively. Other frequently reported symptoms included cardiac, dermatologic, digestive, and ear, nose, and throat disorders. Conclusions and Relevance: In this systematic review, more than half of COVID-19 survivors experienced PASC 6 months after recovery. The most common PASC involved functional mobility impairments, pulmonary abnormalities, and mental health disorders. These long-term PASC effects occur on a scale that could overwhelm existing health care capacity, particularly in low- and middle-income countries.

Gun violence incidence during the COVID-19 pandemic is higher than before the pandemic in the United States.

During the coronavirus disease 2019 (COVID-19) pandemic, gun violence (GV) in the United States (U.S.) was postulated to increase strain on already taxed healthcare resources, such as blood products, intensive care beds, personal protective equipment, and even hospital staff. This report aims to estimate the relative risk of GV in the U.S. during the pandemic compared to before the pandemic. Daily police reports corresponding to gun-related injuries and deaths in the 50 states and the District of Columbia from February 1st, 2019, to March 31st, 2021 were obtained from the GV Archive. Generalized linear mixed-effects models in the form of Poisson regression analysis were utilized to estimate the state-specific rates of GV. Nationally, GV rates were 30% higher between March 01, 2020, and March 31, 2021 (during the pandemic), compared to the same period in 2019 (before the pandemic) [intensity ratio (IR) = 1.30; 95% CI 1.29, 1.32; p < 0.0001]. The risk of GV was significantly higher in 28 states and significantly lower in only one state. National and state-specific rates of GV were higher during the COVID-19 pandemic compared to the same timeframe 1 year prior. State-specific steps to mitigate violence, or at a minimum adequately prepare for its toll during the COVID-19 pandemic, should be taken.

Sudden death in individuals with obstructive sleep apnoea: a systematic review and meta-analysis.

OBJECTIVES: Over 1 billion individuals worldwide experience some form of sleep apnoea, and this number is steadily rising. Obstructive sleep apnoea (OSA) can negatively influence one's quality of life and potentially increase mortality risk. However, the association between OSA and mortality has not been reliably estimated. This meta-analysis estimates the risk of all-cause and cardiovascular mortality in individuals with OSA. DESIGN: Systematic review and meta-analysis. DATA SOURCES: MEDLINE, Cochrane Library, Scopus and Joanna Briggs Institute Evidence-Based Practice databases were searched from inception through 1 January 2020. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: We included observational studies assessing the association of sudden deaths in individuals with and without OSA. DATA EXTRACTION AND SYNTHESIS: Two independent reviewers (AES and ESH) extracted data and assessed the risk of bias using the Newcastle-Ottawa Scale quality assessment tool. Data were pooled using the random-effects models and reported as risk ratios (RRs) with 95% CIs. Heterogeneity was quantified with I2 statistic. RESULTS: We identified 22 observational studies (n=42 099 participants). The mean age was 62 years and 64% were men. OSA was associated with all-cause sudden death (RR=1.74, 95% CI: 1.44 to 2.10, I2=72%) and cardiovascular mortality (RR=1.94, 95% CI: 1.39 to 2.70, I2=32%). A marginally significant dose-response relationship between severity of OSA and the risk of death was observed (p for interaction=0.05): mild OSA (RR=1.16, 95% CI: 0.70 to 1.93), moderate OSA (RR=1.72, 95% CI: 1.11 to 2.67) and severe OSA (RR=2.87, 95% CI: 1.70 to 4.85). Meta-regression analysis showed that older age was a significant contributing factor in the relationship between OSA and mortality. The median study methodological quality was considered high. CONCLUSIONS: OSA is a significant risk factor for all-cause mortality and cardiac mortality. Prevention and treatment strategies to optimise survival and quality of life in individuals with OSA are urgently needed. PROSPERO REGISTRATION NUMBER: CRD42020164941.

Acute Perforated Appendicitis Complicated by Necrotizing Fasciitis and Bladder Perforation.

Acute uncomplicated appendicitis is a common surgical disease that has been well-studied, and its overall mortality has decreased over time. However, delay in treatment can be associated with rare complications such as necrotizing fasciitis, which carries a high mortality rate, and bladder perforation. We present such a case in an 81-year-old female with no significant surgical history who presented to the emergency department with four days of abdominal pain. A CT scan revealed extensive subcutaneous air in the abdominal wall, an inflamed appendix, and a periappendiceal abscess. During subsequent exploratory laparotomy, she was also found to have bladder perforation. She underwent debridement of necrotic tissue of the abdominal wall, appendectomy, drainage of periappendiceal abscess, and bladder perforation repair. She died of septic shock on post-operative day 19, due to gross spillage of urine into the abdomen and ongoing necrotizing fasciitis. Acute perforated appendicitis can lead to rare and fatal complications. Our case presents such a patient with a poor outcome. In approaching a patient with signs of peritonitis, differential diagnoses must remain broad to include late complications such as abscess formation, soft tissue infection, and perforation of surrounding structures.

Renin-angiotensin-aldosterone system inhibitors and the risk of mortality in patients with hypertension hospitalised for COVID-19: systematic review and meta-analysis.

OBJECTIVE: The association between the use of renin-angiotensin-aldosterone (RAAS) inhibitors and the risk of mortality from COVID-19 is unclear. We aimed to estimate the association of RAAS inhibitors, including ACE inhibitors (ACEi) and angiotensin II receptor blockers (ARBs) with COVID-19 mortality risk in patients with hypertension. METHODS: PubMed (MEDLINE) SCOPUS, OVID, Cochrane Library databases and medrxiv.org were searched from 1 January 2020 to 1 September 2020. Studies reporting the association of RAAS inhibitors (ACEi or ARBs) and mortality in patients with hypertension, hospitalised for COVID-19 were extracted. Two reviewers independently extracted appropriate data of interest and assessed the risk of bias. All analyses were performed using random-effects models on log-transformed risk ratio (RR) estimates, and heterogeneity was quantified. RESULTS: Fourteen studies were included in the systematic review (n=73,073 patients with COVID-19; mean age 61 years; 53% male). Overall, the between-study heterogeneity was high (I2=80%, p<0.01). Patients with hypertension with prior use of RAAS inhibitors were 35% less likely to die from COVID-19 compared with patients with hypertension not taking RAAS inhibitors (pooled RR 0.65, 95% CI 0.45 to 0.94). The quality of evidence by Grading of Recommendations, Assessment, Development and Evaluations was graded as 'moderate' quality. CONCLUSIONS: In this meta-analysis, with prior use of RAAS inhibitors was associated with lower risk mortality from COVID-19 in patients with hypertension. Our findings suggest a potential protective effect of RAAS-inhibitors in COVID-19 patients with hypertension. PROSPERO REGISTRATION NUMBER: The present study has been registered with PROSPERO (registration ID: CRD 42020187963).

Predictors of Poor Postoperative Outcomes in Pediatric Surgery Patients in Rural Ghana.

BACKGROUND/PURPOSE: Perioperative complications cause significant pediatric morbidity and mortality in low- and lower middle -income countries. This study investigates factors associated with prolonged length of stay, 90-day readmission and in-hospital mortality among pediatric patients at Eastern Regional Hospital (ERH) in Ghana. METHODS: This is a retrospective review of perioperative morbidity and mortality in children < 18 years at ERH in Koforidua, Ghana. All pediatric surgeries performed between January 2015 and December 2017 were included in this study. Univariate analysis was performed using Pearson's chi-square tests or Fisher's exact tests. Variables that were significant on univariate analysis were included in multivariable logistic regression models adjusted for age and gender. RESULTS: We analyzed 468 patients < 18 years of age with a median length of stay (LOS) of 3 days. The 90-day readmission and in-hospital mortality rates were 138 and 17 per 1000 patients, respectively. The most common procedures were herniorrhaphy (19 %) and appendectomy (15 %). Gastrointestinal surgery, surgical trauma, surgical infection and lack of insurance were significantly associated with prolonged LOS. Young age and female gender were significantly associated with in-hospital mortality. Malaria was significantly associated with 90-day readmission. CONCLUSIONS: Malaria infection is a significant risk factor for readmission, which should be investigated and treated in pediatric surgical patients in rural Ghana. Ensuring that all patients have insurance may result in shorter hospital stays. Provision of laparoscopic equipment may reduce hospital stays for patients undergoing gastrointestinal surgery. Expansion of the surgical work force, particularly pediatric surgeons, could improve perioperative survival in the very young population. LEVEL OF EVIDENCE: Retrospective comparative study.